Intestinal Ultrasound to Assess Disease Activity After Induction With Upadacitinib in Acute Severe Ulcerative Colitis

ABSTRACT

Intestinal ultrasound is a noninvasive, cost-effective tool to assess disease activity in ulcerative colitis (UC). Although upadacitinib, a selective Janus kinase 1 inhibitor, has demonstrated efficacy for induction therapy in patients with moderately to severely active UC, data in acute severe UC remain limited. We report on the use of intestinal ultrasound to assess treatment response after induction with upadacitinib in 3 patients hospitalized with acute severe UC.

INTRODUCTION

Intestinal ultrasound (IUS) is a noninvasive and cost-effective modality for monitoring disease activity in ulcerative colitis (UC). In a study by Voogd et al, bowel wall thickness measured by IUS accurately detected treatment response in patients with moderate to severe UC after 8 weeks of tofacitinib induction when compared to endoscopic assessment.¹ Upadacitinib (UPA) is a selective Janus kinase 1 inhibitor with proven efficacy for induction in moderately to severely active UC, and it is now Food and Drug Administration approved for this indication². There is growing interest in the use of UPA for acute severe UC (ASUC) due to its rapid onset of action, but available data are limited to retrospective uncontrolled studies.³ This case series is the first to show treatment response with IUS after UPA induction in patients hospitalized with ASUC.

CASE REPORT

Case 1

A 19-year-old man with a history of pancolonic UC was admitted with 2 weeks of 10–15 bloody bowel movements daily and a 20-pound weight loss despite outpatient escalation of infliximab to 10 mg/kg every 4 weeks. Laboratory studies were notable for albumin 3.5 gm/dL, ferritin of 10 ng/mL, hemoglobin (Hg) 6.4 gm/dL, and C-reactive protein (CRP) 2.61 mg/L. Stool culture and Clostridioides difficile toxin were negative. He was started on intravenous (IV) steroids. Flexible sigmoidoscopy on day 3 demonstrated Mayo score 2 disease. Biopsies revealed markedly active chronic colitis without viral inclusions, granuloma, or dysplasia. Despite 3 days of IV steroids, he continued to have 5–10 bowel movements with blood, abdominal pain, and urgency with a rising CRP. IUS performed on day 4 showed diffuse wall thickening and increased vascularity with preserved mural stratification involving the sigmoid colon (6.5 mm) and to a lesser extent the descending colon (5 mm) (Figure 1). UPA 45 mg daily was initiated, resulting in marked improvement in symptoms within 4 days, and bowel movements decreased to <5 per day without blood. A repeat IUS on day 8, the same day as discharge, demonstrated significant interval improvement in mural thickening and vascularity of the sigmoid (3.5 mm) and descending (2.5 mm) colon, indicating a favorable treatment response (Figure 1). UPA 45 mg daily was continued for 4 months followed by a transition to 30 mg daily until a repeat colonoscopy was completed approximately 12 months later with endoscopic and histologic remission.

Figure 1.

Case 1 intestinal ultrasound images completed with a Philips EPIQ machine and eL18-4 (5 Hz) straight probe. (A) Transverse gray-scale image of the sigmoid colon before treatment with bowel wall thickness measuring 6.5 mm. (B) Transverse color Doppler ultrasound image of the sigmoid colon demonstrating increased bowel wall Doppler signal (Limberg grade 3). (C) Posttreatment transverse gray-scale image of the sigmoid colon with bowel wall thickness measuring 3.5 mm. (D) Posttreatment transverse color Doppler image of the sigmoid colon demonstrating normal Doppler signal (Limberg grade 1).

Case 2

A 20-year-old woman with a history of pancolonic UC was admitted with 1 month of worsening rectal pain, urgency, and fecal incontinence despite maintenance infliximab 10 mg/kg every 4 weeks. Laboratory evaluation revealed albumin 3.9 gm/dL, CRP 16.97 mg/L, and Hg 11.2 gm/dL. Fecal calprotectin was 6,710 mcg/gm. Patient was started on IV steroids. On day 1, a computed tomography enterography described wall thickening and mucosal enhancement involving the rectosigmoid colon with adjacent stranding. Flexible sigmoidoscopy on day 1 showed Mayo score 3 disease extending to the sigmoid colon. Colon biopsies were negative for cytomegalovirus. IUS on day 2 showed rectal wall thickening (9.3 mm) with marked hyperemia and wall thickening of the sigmoid colon (5 mm) (Figure 2). On day 3, patient was started on UPA 45 mg daily, leading to improvement in her rectal pain the following day. A repeat IUS on day 6, 1 day before discharge, showed a significant interval decrease in rectosigmoid inflammatory changes with residual rectal wall thickening (4.9 mm) without increased Doppler signal and decreased sigmoid wall thickening (2 mm) (Figure 2). Despite initial clinical and sonographic improvement, the patient developed steroid dependence while on UPA 45 mg daily. A repeat colonoscopy 2 months after hospitalization showed Mayo 3 disease in the rectosigmoid junction. Given persistent disease activity, she ultimately underwent total proctocolectomy with ileal pouch anal anastomosis 6 months after starting UPA.

Figure 2.

Case 2 intestinal ultrasound images completed with a Philips EPIQ Elite machine and C5-1 (7 Hz) curved probe. (A) Transverse gray-scale image of the rectum before treatment with bowel wall thickness measuring 9.3 mm. (B) Transverse color Doppler ultrasound image of the rectum demonstrating increased bowel wall Doppler signal (Limberg grade 3). (C) Posttreatment transverse gray-scale image of the rectum with bowel wall thickness measuring 4.9 mm. (D) Posttreatment transverse color Doppler image of the rectum demonstrating normal Doppler signal (Limberg grade 0).

Case 3

A 38-year-old woman with a history of pancolonic UC presented to the emergency department with several months of hematochezia and diarrhea exceeding 20 bowel movements per day with abdominal pain. She was recently started on infliximab 10 mg/kg and had received 2 induction doses without clinical response. Laboratory studies were notable for albumin 2.8 gm/dL, CRP 28.3 mg/L, and Hg 9.1 gm/dL. Stool culture and C. difficile toxin were negative. Fecal calprotectin was 777 mcg/gm. A computed tomography abdomen/pelvis was completed on day 1 showed moderate mural thickening and hyperenhancement extending from the anus to the distal transverse colon. The patient was started on IV steroids. Flexible sigmoidoscopy showed Mayo score 3 disease extending from the rectum to the cecum. IUS revealed active inflammation of the rectum with bowel wall thickening (8.9 mm), hyperemia and perirectal edema as well as bowel wall thickening of the sigmoid colon (5 mm), and increased Doppler signal in the descending colon (Figure 3). Given no improvement on day 3 and patient's desire to avoid surgery, UPA 45 mg daily was started. By day 8, patient's bowel movements had decreased to fewer than 10 per day with near-complete resolution of her abdominal pain. A repeat IUS on day 8, 1 day before discharge, demonstrated persistent rectal wall thickening (7 mm) and mucosal hyperemia but interval resolution of previously identified inflammatory changes in the sigmoid and descending colon (Figure 3). The wall thickening in the sigmoid colon was normal (3 mm), and there was no increased Doppler signal in the descending colon. A fecal calprotectin 9 months after hospitalization was 17 mcg/gm. A repeat colonoscopy 1 year after hospitalization showed endoscopic and histologic remission.

Figure 3.

Case 3 intestinal ultrasound images completed with a Canon Aplio i800 machine i8CX1 probe (images A, B) and endovaginal 11C3 probe (images C, D). (A) Transverse gray-scale image of the rectum before treatment with bowel wall thickness measuring 8.9 mm. (B) Transverse color Doppler ultrasound image of the rectum demonstrating increased bowel wall Doppler signal (Limberg grade 2). (C) Posttreatment transvaginal gray-scale image of the rectum with bowel wall thickness measuring 7 mm. (D) Posttreatment transvaginal color Doppler image of the rectum demonstrating persistently high Doppler signal (Limberg grade 2).

DISCUSSION

UPA has shown to provide rapid symptom relief with improvement in IUS parameters in patients with ASUC. Vermeire et al demonstrated that UPA 45 mg daily significantly improved symptoms as early as day 1.⁴ This rapid onset of action is advantageous in ASUC, especially after antitumor necrosis factor α treatment failure, although data in this setting remain limited.^3,5 This case series is the first to demonstrate treatment response using IUS after induction with UPA in patients with ASUC, supporting IUS as a noninvasive, cost-effective modality for monitoring disease activity.⁶ Moreover, UPA may represent a potential salvage treatment for patients with ASUC refractory to antitumor necrosis factor agents. These findings underscore the need for larger, prospective studies to further evaluate both the efficacy of UPA in ASUC and the role of IUS in monitoring treatment response in this population.

DISCLOSURES

Author contributions: E. Gibson, KB Russ, and L. Shipley: manuscript development and editing; J. Perchik: imaging and manuscript development; MS Ismail: project development and manuscript completion and is the article guarantor.

Financial disclosure: None to report.

Previous presentation: One case from this case series has been presented at AIBD 2023, December 2023; Orlando, Florida.

Informed consent was obtained for this case report.

ABBREVIATIONS:

ASUC

acute severe ulcerative colitis

CRP

c-reactie protein

IUS

Intestinal ultrasound

UC

ulcerative colitis

UPA

upadacitinib